Chapter 120 – Coats’ Disease and Retinal Telangiectasia
JULIA A. HALLER
• A localized, congenital, retinal vascular disorder that consists of abnormal telangiectatic segments of blood vessels that result in leakage.
• Retinal telangiectasia.
• Retinal capillary nonperfusion.
• Dilated intercapillary spaces.
• Lipid exudate.
• Subretinal fluid.
• Usually unilateral.
• Male predominance.
• Fibrovascular macular scars.
Retinal telangiectasia is found in a wide range of ocular disease processes. Most retinal telangiectases are acquired secondary to local or systemic conditions, as, for example, in branch retinal vein occlusion and diabetic retinopathy. These disorders should be considered in the differential diagnosis when alterations are seen in the retinal vasculature and should be excluded before primary retinal telangiectasia is diagnosed. Primary retinal telangiectasia is found in Coats’ disease, Leber’s miliary aneurysms (a localized, less severe form of Coats’ disease), idiopathic juxtafoveal telangiectasia, and other angiomatous diseases.
Coats’ disease, an idiopathic condition characterized by retinal vascular changes and exudation, was first described by Coats in 1908. In 1912 Leber reported his series of patients who had multiple miliary aneurysms and retinal degeneration. In 1915 Leber wrote two more articles and concluded that the disease he had described in 1912 was a variant of Coats’ disease.
Coats’ disease is characterized by discrete zones of alteration in the retinal vascular structure with aneurysmal dilatation, capillary dropout, and leakage. Vision may decrease as a result of leakage from the abnormal vascular channels that are formed, with consequent edema, lipid deposition, and exudative retinal detachment. The disease affects men three times as often as women, has no reported racial or ethnic predilection, and is usually unilateral, although as many as 10–15% of cases may be bilateral. The average age at diagnosis is 8–16 years, although the disease has been described in patients as young as 4 months. About two thirds of juvenile cases present before age 10 years; approximately one third of patients are 30 years or older before symptoms begin. Coats’ disease does not appear to be inherited.
The typical ophthalmoscopic picture of Coats’ disease is one of retinal vascular abnormalities associated with localized lipid deposition and varying degrees of subneural retinal exudate ( Fig. 120-1 ). Vessels may appear sheathed and telangiectatic, and they may have aneurysms that are grape-like, clustered, or lightbulb shaped; often, the vessels are adjacent to areas that lack normal capillaries ( Fig. 120-2 ). The severity of vascular malformation parallels the degree of surrounding neural retinal thickening, exudation, hemorrhage, and destruction of small vessels. Aberrant arteriovenous communicating channels are frequently present, and occasionally true retinal neovascularization occurs. Leakage from the abnormal vascular bed produces a cloudy subretinal exudate, which gravitates toward the posterior pole. As the serous component of the exudate is resorbed by retinal vessels, the lipid-rich yellowish component is left beneath and within the outer neural retinal layers. Over long periods, this yellow exudate may stimulate the ingrowth of blood vessels and fibrous scar tissue ( Fig. 120-3 ). The vascular abnormalities occur more commonly superotemporally; they also are found in the macular and paramacular areas. On average, two quadrants of retina are found to be affected at the initial diagnosis in older patients, but young patients may have more serious disease and more extensive retinal involvement. In more advanced and severe cases
Figure 120-1 Coats’ disease. Note the typical vascular abnormalities with aneurysmal dilatation, telangiectasia, exudation, and severe lipid deposition in the macula.
of Coats’ disease, exudative retinal detachment develops ( Fig. 120-4 ). Cells in the vitreous are common.
The clinical course is variable but generally progressive. Acute exacerbations of the disease may be interspersed with more quiescent stages. Spontaneous remissions have been reported, with spontaneous occlusion of the vessels and resorption of the exudate, but these are the exception. Choroidal neovascularization may occur in areas of lipid deposition. Secondary complications include neovascularization, vitreous hemorrhage, cataract, rubeosis iridis, and neovascular glaucoma, with phthisis bulbi in severe cases.  
In children, Coats’ disease is typically diagnosed as a result of the recognition of poor vision, strabismus, or leukokoria. In patients with leukokoria, a white pupillary reflex on photographs may be the initially noted abnormality. (The disorder is picked up most frequently by parents or pediatricians or on routine school vision screening.) In these cases, the disease is usually advanced already, with extensive lipid deposition and retinal detachment (see Fig. 120-4 ). In adults, the most common presenting complaint with Coats’ disease is poor vision; in these cases, the disease may be much more limited in extent.
Figure 120-2 Vessels may appear sheathed, dilated, and telangiectatic or feature grape-like bunches of aneurysms. Vascular changes that are saccular and lightbulb shaped may be seen as well.
Figure 120-3 Long-standing submacular exudate. This may stimulate ingrowth of blood vessels or fibrous tissue, with retinal pigment epithelium migration and hyperplasia and the formation of fibrous scars.
The anterior segment examination findings are normal in all but the most advanced cases of Coats’ disease, in which rubeosis iridis, angle-closure glaucoma, and cataract may be present. The diagnosis is confirmed ophthalmoscopically when the typical vascular abnormalities are seen in association with lipid deposition and subretinal exudate. The retinal vascular abnormalities occur in small clusters and include kinked, looped, tortuous, and sheathed vessels of varied and irregular caliber.
Fluorescein angiography is a useful tool for delineating the nature and extent of the vascular abnormalities present in this disease. Most commonly, numerous areas of telangiectasia and micro- and macroaneurysm formation are seen, with beading of blood vessel walls and anomalous vascular communicating channels ( Fig. 120-5 ). Early and persistent dye leakage documents the source of exudation and hemorrhage.   The microvasculature may be diffusely absent, with areas of complete capillary nonperfusion.
The severe juvenile form of Coats’ disease, which presents with exudative retinal detachment, must be differentiated from other diseases that cause leukokoria in childhood, including retinoblastoma,
Figure 120-4 In children, Coats’ disease may present as leukokoria, with advanced lipid deposition and exudative retinal detachment. In this eye, the anterior chamber is shallowed slightly, and the retina is immediately behind the lens.
Figure 120-5 Fluorescein angiography of Coats’ disease. In this eye, extensive vascular changes are seen to extend temporally from the macula, with zones of telangiectasia and aneurysm formation adjacent to a large area of capillary nonperfusion. Beading of the blood vessel walls and anomalous vascular communicating channels are present.
retinopathy of prematurity, retinal detachment, persistent hyperplastic primary vitreous, congenital cataract, toxocariasis, incontinentia pigmenti, Norrie’s disease, and familial exudative vitreoretinopathy. Gass has pointed out that telangiectatic vessels may appear on the surface of both retinoblastomas and Coats’ disease lesions. In retinoblastoma, these dilated vessels are continuous with the large vascular trunks that extend into the tumor; in Coats’ disease, the dilated vessels do not extend into the subretinal mass. Fluorescein angiography may help differentiate the two entities. The diagnostic modalities used most commonly are ultrasonography and computed tomography (CT), because of their ability to pick up calcium deposits in retinoblastomas.
Ultrasonography is a convenient, noninvasive test that may distinguish between Coats’ disease and retinoblastoma, as well as other entities. The retinal detachment in Coats’ disease typically is exudative in appearance, with an absence of the calcifications seen in retinoblastoma. CT may help characterize intraocular morphology, quantify subretinal densities, and identify vascularity within the subretinal space, through the use of contrast enhancement. Also, CT may help detect other abnormalities within the orbit or intracranial space. For optimal resolution, multiple thin slices before and after contrast induction are recommended. Magnetic resonance imaging (MRI) is a useful ancillary test because it permits multiplanar imaging and superior contrast resolution, and it may provide information about the biochemical makeup of tissues. However, MRI is less useful for the detection of calcium than either ultrasound or CT scanning, but it has been shown to help differentiate retinoblastoma from Coats’ disease, toxocariasis, and persistent hyperplastic primary vitreous. High-resolution Doppler ultrasonography occasionally may be of use as an adjunctive diagnostic modality. This technique provides real-time imaging; duplex pulse Doppler evaluation may delineate structural abnormalities that are not shown by other testing modalities. Serum lactate dehydrogenase and isoenzyme levels have not proved useful in distinguishing between Coats’ disease and retinoblastoma. Examination of subretinal fluid is used rarely, but it confirms the diagnosis of Coats’ disease on the basis of cholesterol crystals and pigment-laden macrophages in the absence of tumor cells.
Less severe stages of Coats’ disease, especially in adults, must be differentiated from other disorders that produce vascular changes and exudation; these include inflammatory disorders such as Eales disease, vasculitis, and collagen vascular disease. Tumors accompanied by exudation may mimic Coats’ disease, as may diabetic vasculopathy with lipid deposition, branch retinal vein occlusion with vascular remodeling and edema, rhegmatogenous retinal detachment, radiation retinopathy, idiopathic juxtafoveal telangiectasia, von Hippel’s disease, angiomatosis of retina, exophytic capillary hemangioma, and sickle-cell retinopathy. In these cases, a thorough review of the systems and medical and family histories usually help differentiate primary from secondary disorders. Fluorescein angiography and, occasionally, echography also may be of use.  
Idiopathic Juxtafoveal Retinal Telangiectasia
Idiopathic juxtafoveal retinal telangiectasia is a group of disorders initially described by Gass and Oyakawa in 1982. The disease is characterized by onset in adulthood and presentation with mild blurring of central acuity caused by exudate from ectatic retinal capillaries in the juxtafoveal region of one or both eyes. They divided these patients into four categories: groups 1A, 1B, 2, and 3. 
Group 1A disease consists of unilateral congenital parafoveal telangiectasia, which typically occurs in men and affects only one eye. Retinal vascular abnormalities are present in a small area, one to two disc areas in diameter, in the temporal half of the macula. Onset of symptoms, with visual loss in the 20/40 (6/12) or better range, typically develops at a mean age of 40 years. Photocoagulation of areas of leakage may help restore acuity.
Group 1B disease consists of unilateral idiopathic parafoveal telangiectasia, usually found in middle-aged men who have blurring caused by a tiny area of capillary telangiectasia confined to one clock hour at the edge of the foveal avascular zone. Vision is usually 20/25 (6/7) or better. Photocoagulation usually is not considered for these eyes because of the proximity of the leakage to the fovea and the good prognosis without treatment. The lesion may be acquired or may simply be a very small focus of congenital telangiectasia.
Group 2 disease consists of bilateral, acquired, idiopathic parafoveal telangiectasia. This variant affects patients in the fifth and sixth decades; mild blurring of vision occurs in one or both eyes. The patients typically have small, symmetrical areas of capillary dilatation, usually the size of one disc area or less, in both eyes. The vascular changes may be temporal only or may include all or part of the parafoveolar nasal retina as well. No lipid is deposited, and minimal serous exudation is present. A hallmark is the characteristic gray appearance of the lesions on biomicroscopic examination, with occasional glistening white dots in the superficial retina. Red-free photography often highlights these findings best ( Figs. 120-6 and 120-7 ). These patients also commonly have right-angled retinal venules that drain the capillary abnormalities and are present in the deep or outer retinal layers. Retinal pigment epithelial hyperplasia eventually
Figure 120-6 Bilateral idiopathic parafoveal telangiectasia can often best be demonstrated with red-free photography. This eye features capillary abnormalities present for virtually 360° in the parafoveal area.
Figure 120-7 Early transit of the eye shown in Figure 120-6 demonstrates a plexus of capillary abnormalities ringing the fovea.
tends to develop along these venules. In these patients, slow loss of visual acuity over many years is produced by atrophy of the central fovea; patients also may develop choroidal neovascularization, hemorrhagic macular detachment, and retinochoroidal anastomosis. Photocoagulation may be of benefit, but in most cases, the abnormal lesions are so close to the fovea that treatment is problematical, and choroidal neovascularization, if it develops, is often subfoveal.
Bilateral idiopathic perifoveal telangiectasia with capillary occlusion is a rare variant in which adults experience loss of vision because of progressive obliteration of the capillary network, which begins with telangiectasia. The capillaries’ aneurysmal malformations are more marked than in the other, milder forms of the disease; no leakage occurs from the capillary bed.
Isolated case reports have described a number of other diseases that occurred simultaneously in patients with Coats’ disease. In many cases, it is doubtful that an actual causal association exists. These diseases include retinitis pigmentosa, muscular dystrophy, deafness, mental retardation, central nervous system dysfunction, Senior-Loken syndrome, the ichthyosis hystrix variant of epidermal nevus syndrome, and Turner’s syndrome. Gass described a patient who had a facial angioma and typical retinal telangiectasia, and another who had bilateral retinal disease and progressive facial hemiatrophy. Bilateral telangiectasia and Coats’ syndrome have been reported in multiple family members who have facioscapulohumeral muscular dystrophy and deafness. No definite connection, however, has been made between other systemic or ocular conditions and Coats’ disease, and no clear evidence exists of genetic transmission. The adult form of the disease has been described as frequently associated with hypercholesterolemia, although such an association does not occur in the juvenile form. 
Histopathologically, Coats’ disease has been studied intensively because of the number of enucleations formerly performed for suspected intraocular tumors. Eyes with Coats’ disease demonstrate marked thickening of the basement membrane of the telangiectatic vessels, as demonstrated by deposition of periodic acid-Schiff (PAS)–positive material. Irregular dilatation of the retinal vessels is seen, often associated with massive exudation of PAS-positive material into the outer neural retinal layers ( Fig. 120-8 ). This exudate produces variable amounts of degeneration
Figure 120-8 Histopathological section of an eye with Coats’ disease. Note the marked neural retinal edema, dilated and aneurysmal vascular channels (with PAS-positive material in their walls), and intra- and subneural retinal exudate. (Courtesy of W. R. Green, MD.)
and disruption of the neural retinal architecture. Lipid-laden macrophages are present beneath and in the outer layers of the neural retina. Glial cells and retinal pigment epithelium cells may migrate in, surround, and wall off the lipid-laden subretinal exudate, which results in the formation of macular and subretinal nodules. Marked retinal endothelial proliferation and hemorrhagic infarction may occur. 
The major goal of treatment in Coats’ disease is to preserve or improve visual acuity or, when this is impossible, to preserve the anatomical integrity of the eye. Intervention is contemplated when exudation is extensive and progressive, threatens central acuity, or produces significant peripheral retinal detachment. In severe, untreated cases, total retinal detachment, iris neovascularization with glaucoma, and phthisis bulbi can result. Treatment of Coats’ disease is directed toward closure of the abnormal, leaking retinal vessels to allow resorption of exudate. Restoration of vision may be a difficult goal to achieve; in many cases, the visual results are poor even with successful treatment, especially when the macula is involved initially in the exudative process.    
Laser photocoagulation is the treatment of choice in mild to moderate cases of exudation from Coats’ disease. Fluorescein angiographic guidance allows precise, localized treatment of the leaking aneurysms and vessels. Early photocoagulation trials used the xenon arc laser to produce resolution of exudate. The most extensive clinical experience has been with the argon blue-green laser, but more recently, clinicians have employed wavelengths of light better absorbed by hemoglobin, such as the argon green-yellow and the diode green. Lesions that leak are treated directly with relatively large (200–500?µm) applications of moderate-intensity light ( Fig. 120-9 ). Scatter photocoagulation to areas of extensive nonperfusion are of unproved value but may lessen the chance of secondary neovascularization. Peripheral lesions may be treated with the indirect laser if they are inaccessible via the contact lens and slit-lamp delivery system. The indirect laser is also a useful modality in children, who frequently need to be treated under general anesthesia.
Cryotherapy and diathermy are of use in the ablation of abnormal retinal vessels in Coats’ disease. In cases of exudative detachment, a trans-scleral mode of energy delivery is preferred; cryotherapy is the modality most commonly used. Where subretinal fluid is present, cryotherapy to the anomalous vessels is recommended using a single freeze or freeze-refreeze technique.
Figure 120-9 Initial photocoagulation of the eye shown in Figure 120-5 . Large, medium-intensity spots have been placed on leaking aneurysms, sparing the foveal avascular zone at first. More peripherally, photocoagulation covers temporal aneurysms and is also placed in a scatter pattern in zones of nonperfusion.
Figure 120-10 Technique used for drainage of subretinal fluid in eyes with extensive exudative detachment. The pediatric infusion cannula is sutured into the anterior chamber through a limbal stab incision with a single Vicryl suture. This is placed in a convenient quadrant so that the eye can be rotated and a posterior draining sclerotomy fashioned. The infusion runs into the anterior chamber and around intact lens zonules, keeping the eye formed as voluminous quantities of thick, yellow subretinal fluid are drained; this subretinal fluid is speckled with cholesterol and lipid deposits.
If the retina is highly elevated, it may be necessary to drain subretinal fluid in order to flatten the retina and allow sufficient freeze to reach the retinal vessels. In these cases, the retina is flattened, the eye reformed, and cryotherapy or laser applied ( Fig. 120-10 ). Subretinal pigmentation and fibrosis usually ensue and follow the lipid resolution. If this involves the macula, visual return is commensurately poor.
Another approach to eyes that have significant retinal detachment is to perform a scleral buckling procedure, which involves dissection of a scleral bed in the area of the abnormal vessels, application of diathermy with drainage of subretinal fluid in the bed, and silicone buckle implantation. In all four of the cases so treated, successful reattachment was achieved, and the exudation gradually resorbed as the abnormal vasculature disappeared, without, however, any return of vision. Harris reported that a scleral buckle sometimes aids the application of postoperative photocoagulation, because it can be oriented beneath the abnormal vessels, and anomalies at the apex of the buckle can be treated effectively, with residual subretinal fluid remaining elsewhere. Siliodor et al.  reported a series of 13 children (who had blind eyes and bullous exudative detachments) followed either after no treatment or after surgery that involved intraocular infusion, drainage of subretinal fluid, and cryotherapy on one or more occasions. Of the six untreated eyes, four developed painful neovascular glaucoma and underwent enucleation. The seven treated with surgery all remained cosmetically acceptable and comfortable; none developed neovascular glaucoma.
In selected cases of Coats’ disease with intravitreal proliferation and traction detachment, vitreous surgery may improve the clinical course. Machemer and Williams reported successful results with surgical removal of vitreal and preretinal membranes and destruction of leaking vessels in a small series of patients. Other authors have also reported some success, again in end-stage eyes, with vitrectomy, transvitreal drainage of subretinal fluid, and extensive photocoagulation or cryotherapy to prevent neovascular glaucoma.
Repeated therapeutic laser or cryotherapy treatments may be required in eyes that have Coats’ disease. Most patients require at least two treatments. Exudate typically begins to resorb within 6 weeks of treatment, if the abnormal vasculature has been eliminated. Depending on the amount of lipid accumulation, in many cases, it takes months to more than a year for complete resolution. Successful treatment is accomplished more easily in eyes that have fewer quadrants with affected vasculature. Recurrence of exudate after initially successful treatment signals the development of new abnormal leaking vessels; these must be searched out meticulously. Contact lens biomicroscopy with a three-mirror lens sometimes is a useful adjunct to indirect ophthalmoscopy in these cases, as is fluorescein angiography with careful sweeps of the retinal periphery. Recurrences may occur years after initially successful treatment, so it is particularly important to follow juvenile patients who may develop significant problems if left unattended. Egerer et al.  recommended that all patients who have Coats’ disease should be examined at least twice a year to catch any early recurrent problems that may develop in a small percentage of these patients.
COMPLICATIONS OF TREATMENT
Complications of photocoagulation and cryotherapy for Coats’ disease include inflammation; hemorrhage; chorioretinal anastomosis formation; and retinal, chorioretinal, and subretinal fibrosis. Macular distortion secondary to epiretinal membrane formation and contraction has been reported following photocoagulation for Coats’ disease and may occur even if the disease is untreated. Gass reported one adult patient who developed total retinal detachment and proliferative vitreoretinopathy after cryotherapy for peripheral retinal telangiectasia that was discovered late in life; the eye initially had 20/20 (6/6) acuity.
With intraocular surgical intervention, additional risks include cataract formation, choroidal hemorrhage, retinal detachment, endophthalmitis, glaucoma, and phthisis.
COURSE AND OUTCOME
The clinical course in Coats’ disease is variable, but it is usually progressive if left untreated. Continued exudation from abnormal vascular channels produces a gradual accumulation of lipid and serous retinal detachment. The downhill course is more rapid in eyes with more extensive vascular abnormalities. Acute exacerbations of the disease may occur, with intervening periods of relative stability. Occasional remissions, produced by spontaneous occlusion of the vessels, have been reported. The end stage of the exudative process, seen in eyes with severe Coats’ disease and particularly in young patients who have an early onset of symptoms, is total retinal detachment, which may be followed by rubeosis iridis, neovascular glaucoma, and eventually phthisis bulbi.
The ultimate prognosis for eyes with Coats’ diseases can be measured in terms of two end points: visual acuity and anatomical stability. Unfortunately, central visual acuity is frequently poor in eyes with Coats’ disease, because the disease is not diagnosed and treated until after significant macular lipid deposition is present. Even with good treatment and resolution of the macular deposits, significant subretinal fibrosis and macular impairment are present. Despite this, amblyopia therapy should be considered in young patients who have Coats’ disease. Optical penalization or occlusion of the better eye can result in significant visual improvement in the diseased eye, with gains in acuity to the 20/60–20/100 (6/18–6/30) range after resorption of macular exudate.
Visual acuity results may be quite good in patients who have very mild vascular anomalies that do not require treatment or are discovered and treated before the macula is involved by the exudative process. It is difficult to estimate the frequency with which this situation develops in the general population, because reported series discuss only more severe cases referred to tertiary treatment centers, and the disease is rare enough to have avoided scrutiny in population-based studies.
Eyes with severe exudation and retinal detachment rarely retain vision better than 20/400 (6/120), and many see much worse than this. Nevertheless, successful treatment of leaking vascular channels may salvage some vision, and this has the advantage of stabilizing the eye anatomically. Occasionally an eye may be saved structurally without light perception.
The prognosis for retaining anatomical integrity of the globe is much better. The worst outcomes are in juvenile cases of total retinal detachment. With modern diagnostic improvements, these eyes are now rarely removed when a tumor is suspected, but some cannot be rehabilitated and go on to phthisis or enucleation. Most eyes with Coats’ disease, however, can be saved. Despite chorioretinal scarring, most eyes are cosmetically acceptable, grow and develop otherwise normally, and in many cases have useful vision. Amblyopia therapy, strabismus surgery, and other types of ancillary rehabilitation may be useful and should not be neglected as part of the total treatment of these patients.
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